Hysterectomies Fail and Fall Down Again
Obstet Gynecol. Author manuscript; bachelor in PMC 2012 Dec ane.
Published in concluding edited form as:
PMCID: PMC3223258
NIHMSID: NIHMS330938
Effect of Hysterectomy With Ovarian Preservation on Ovarian Function
Patricia Chiliad. Moorman
1Cancer Prevention, Detection and Control Enquiry Plan, Section of Community and Family Medicine, Duke University Medical Center, Durham, NC
Evan R. Myers
iiDepartment of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC
Joellen Thou. Schildkraut
oneCancer Prevention, Detection and Control Enquiry Program, Department of Customs and Family Medicine, Duke Academy Medical Heart, Durham, NC
Edwin S. Iversen
3Department of Statistical Scientific discipline, Duke University, Durham, NC
Frances Wang
aneCancer Prevention, Detection and Control Research Programme, Department of Community and Family Medicine, Duke Academy Medical Center, Durham, NC
Nicolette Warren
iCancer Prevention, Detection and Control Research Program, Department of Community and Family unit Medicine, Duke Academy Medical Eye, Durham, NC
Abstruse
Objective
To prospectively judge the risk for before ovarian failure among women undergoing hysterectomy with ovarian preservation, as compared to women of like historic period without hysterectomy.
Methods
A prospective cohort study was conducted among women aged thirty to 47 years undergoing hysterectomy without bilateral oophorectomy (n=406) and women with intact uteri (due north=465). Blood samples and questionnaire information were obtained at baseline and annually for up to 5 years. Hazard ratios (HR) for ovarian failure, defined as follicle-stimulating hormone (FSH) levels 40 IU/L or college, were calculated using Cox proportional hazards models.
Results
Ovarian failure occurred among sixty of the women with hysterectomy and 46 of the control women. Women undergoing hysterectomy were at nearly a twofold increased risk for ovarian failure as compared to women with intact uteri (HR=1.92, 95% confidence interval (CI) 1.29 – 2.86). The proportional hazards model further estimated that 14.viii% of women with hysterectomy experienced ovarian failure after four years of follow-up compared to 8.0% of the control women. Risk for ovarian failure was greater for women who had a unilateral oophorectomy along with their hysterectomy (HR=2.93, 95% CI i.57 – 5.49), merely likewise was significantly increased for women who retained both ovaries (HR=1.74, 95% CI 1.xiv – 2.65).
Conclusions
Increased risk of before ovarian failure is a possible consequence of premenopausal hysterectomy. While information technology is unresolved whether it is the surgery itself or the underlying condition leading to hysterectomy that is the cause of before ovarian failure, physicians and patients should take into account this possible sequela when considering options for handling of benign weather of the uterus.
INTRODUCTION
Hysterectomy is the most mutual not-obstetrical surgical procedure among women in the United States. Although the increasing number of procedures performed in convalescent settings makes interpretation from hospital-based registries difficult, sources report from 460,000 to 600,000 procedures annually in the The states.(one, 2) Data from the Behavioral Adventure Factor Surveillance Organization show that more than ane-quarter of American women aged xviii to 75 have had a hysterectomy, and it is estimated that upwardly to 40% of women will have a hysterectomy during their lifetimes. (3, 4) Although uterine avenue embolization, endometrial ablation or progestin-releasing intrauterine devices are increasingly used for treating common indications for hysterectomy such every bit fibroids and dysfunctional uterine bleeding, hysterectomy rates remain high, (i) and the long-term outcomes after surgery are an important clinical consideration.
An unresolved concern with hysterectomy is whether it increases take chances for early menopause. More than half of all hysterectomies are performed on women younger than age 44, with the highest rates among women aged 40 to 44 years.(5) The majority of women having pre-menopausal hysterectomies retain at least ane ovary (5) because of evidence that the physical and psychological benefits derived from keeping the ovaries outweigh the possibility of ovarian pathology, including cancer.(vi, 7) Although it is clear that nigh women exercise non lose ovarian function in the brusk-term after hysterectomy without bilateral oophorectomy, there has long been suspicion that these women are at increased risk for early on ovarian failure.(viii) Earlier menopause in turn has serious health implications including increased take chances for osteoporosis, cardiovascular disease and all-crusade mortality.(9-13)
The association betwixt hysterectomy and early menopause has been examined in a number of studies dating back several decades, but most of them had important limitations including cross-sectional or retrospective study designs, lack of a control group, menopause classification based only on symptoms, small sample sizes or insufficient follow-up fourth dimension. (eight, 14-22) In the one prospective study with long-term follow-up and serial hormone measurements that evaluated risk for menopause among women having a hysterectomy (n=257) every bit compared to women of similar historic period with intact uteri (n=258), Farquhar and colleagues estimated that menopause occurred nearly iv years earlier in women undergoing hysterectomy every bit compared to women who did not take the surgery.(20)
In this report nosotros estimate the take chances of before ovarian failure (defined equally a serum follicle stimulating hormone (FSH) ≥ xl IU/L) after pre-menopausal hysterectomy using data from a prospective study of ovarian function subsequently hysterectomy conducted in Due north Carolina.
METHODS
Study subjects were pre-menopausal women in a prospective cohort known as the PROOF (Prospective Research on Ovarian Function) Written report. Methods for the report have been described previously.(23) Betwixt 2004 and 2007, nosotros identified women scheduled to undergo hysterectomy from operating room schedules of the 2 hospitals in Durham, NC, both of which are office of the Duke University Health Organisation. Potentially eligible women received a letter from their physician describing the study and informing them that an interviewer would be contacting them to ask them to take part. The interviewer verified that the women met the eligibility criteria of historic period 30 to 47 years, were pre-menopausal equally evidenced by at least one menstrual menstruum in the previous iii months, had no personal history of cancer (except not-melanoma skin cancer), were able to complete an interview in English and at least 1 ovary was expected to be left intact after the hysterectomy. Eligible women who agreed to participate were scheduled for an interview visit during which they signed an informed consent form, completed an interviewer-administered questionnaire, had a claret specimen drawn and had body measurements taken (height, weight, waist circumference and hip circumference). All baseline visits occurred before the women'southward hysterectomies, and most were done in conjunction with their pre-operative visits. The study subjects were re-contacted annually for follow-upwardly visits to obtain updated questionnaire information and blood samples.
Command women were recruited using study brochures and ads in publications that were placed in clinics and offices of gynecology and family unit medicine practices within Knuckles University Wellness System. The eligibility criteria were age 30 to 47 years, pre-menopausal, no personal history of cancer, non currently pregnant and able to complete an interview in English. Recruitment was targeted such that the age distribution was like to that of the cases and the race distribution was similar to that of Durham County. Baseline and follow-up interview visit procedures for the control women were the same as for the women undergoing hysterectomy. The study protocol was approved by the Duke University Medical Center Institutional Review Board.
Information obtained from the questionnaires included demographic characteristics, menstrual cycle characteristics, pregnancy history, history of contraceptive and hormone employ, menopause symptoms, current employ of medications and supplements and lifestyle characteristics such every bit smoking history and alcohol consumption. Clinical information for the women undergoing hysterectomy including type of surgery, pre- and post-operative diagnoses and pathologic data was abstracted from the medical records.
Blood samples obtained from the study subjects were spun down, the serum was divided into two or more aliquots depending on the volume obtained and the tubes were stored in a −eighty°C freezer until the fourth dimension of analysis. All samples were analyzed for FSH at the Duke Clinical and Research Laboratories, which serves as the core laboratory for all general testing requirements for Duke Hospital and Clinics. The samples were analyzed in batches with samples from the women with hysterectomies and control women intermixed in each batch. Laboratory personnel were blinded to hysterectomy status.
A total of 902 women scheduled for hysterectomy were identified for the study. We were unable to contact or schedule an interview with 58 women before their surgery and 145 women were institute to be ineligible (73 were planning to have a bilateral oophorectomy, 27 had a prior history of cancer, 14 decided against hysterectomy, and 31 did not meet other the eligibility criteria including age, ability to complete an interview in English language, or menstrual periods in prior three months). Of the 699 women who were contacted and eligible, baseline surveys and blood samples were obtained from 504 (72.1%). Of these 504 women, nosotros excluded from assay those for whom medical record review later on their surgery showed that they were ineligible due to bilateral oophorectomy or a cancer diagnosis (n=45), those with a baseline FSH value 40 IU/L or college (n=half-dozen), and those who did not complete any follow-upwards visits (northward=47), for a total of 406 women with hysterectomy included in the analysis.
Baseline interviews and claret samples were obtained from 518 control women. We excluded from our analysis women with baseline FSH values ≥ xl IU/L (n=15), women who did not complete whatsoever follow-up visits (n=31), and women with a cancer diagnosis (n=half dozen) or bilateral oophorectomy (n=1) during the first twelvemonth of follow-up. The final number of command women included in the analysis was 465. When comparing characteristics of the women nosotros excluded to those included in the study, we found no statistically significant differences except that the excluded controls had a lower educational level and were more than likely to be electric current smokers.
Follow-up of the cohort continued until November 2009. The median number of blood draws (baseline and follow-upwardly) was four and the maximum was vi. Women enrolled every bit controls who afterwards had a hysterectomy were censored at the time of their surgery. Likewise, women were censored if they had a bilateral oophorectomy or a diagnosis of cancer. The main effect of ovarian failure was divers every bit an FSH value ≥ 40 IU/L.
The racial composition of the cohort was 48.9% White, 47.v% African American and 3.6% other races. For race-specific results, we conducted analyses comparison African American women to White women and African American women to all other races. Because the results were substantively the same in these analyses, the results presented in this paper compare African American women to all other races.
Statistical Analyses
Comparisons between women with hysterectomy and controls and between racial groups were made with t-tests for continuous variables and chi-foursquare or Fisher's exact test for categorical variables. Kaplan-Meier plots were used to testify the time to ovarian failure comparison women with and without hysterectomy. Cox proportional take a chance modeling was performed to calculate the hazard ratios (Hour) and 95% confidence intervals (CI) for ovarian failure. Variables that are established predictors of menopause or were associated with risk for ovarian failure in bivariate analyses were included in multivariable models. The proportional hazards supposition was tested by evaluating interactions between the variables of concern and log (time). None of the fourth dimension-dependent variables was significant, supporting the assumption of proportional hazards. Analyses were performed using SAS statistical software, version 9.2 (Cary, NC).
RESULTS
Descriptive characteristics of women undergoing hysterectomy and controls for the total study population and stratified by race are presented in Tabular array 1. Women undergoing hysterectomy were more likely than controls to exist parous and accept a history of tubal ligation. No statistically significant differences were observed for historic period at menarche, history of cesarean delivery, history of infertility or duration of oral contraceptive utilize. In the overall group, torso mass alphabetize was higher amongst the women undergoing hysterectomy than controls, with significant differences amid non-African Americans but not among African American women. Every bit would be expected, a greater proportion of women undergoing hysterectomy reported a history of uterine fibroids, endometriosis, ovarian cysts and myomectomy, with some differences by race. Uterine fibroids and a prior history of myomectomy were more commonly reported by African American women, whereas a history of endometriosis or ovarian cysts was more common among non-African Americans. Baseline FSH values were not significantly different between women undergoing hysterectomy and controls, or between African Americans and non-African Americans.
Table ane
Baseline Characteristics of Women Undergoing Hysterectomy and Controls, for Full Study Population and Stratified by Race
| All Women | Non-African American Women | African American Women | |||||||
|---|---|---|---|---|---|---|---|---|---|
| | |||||||||
| Hysterectom | Command | Hysterectom | Control | Hysterectomy | Control | ||||
| y n=406 (%) | n=465 (%) | P | y n=199 (%) | n=264 (%) | P | n=207 (%) | north=201 (%) | P | |
| Historic period category (years) | |||||||||
| thirty – 34 | 5.9 | 9.0 | 0.2 | eight.0 | nine.8 | 0.eight | 3.9 | eight.0 | 0.04 |
| 35 – 39 | 24.four | 26.9 | 27.one | 24.2 | 21.7 | xxx.3 | |||
| 40 – 44 | 43.one | 37.9 | 38.2 | 37.5 | 47.8 | 38.3 | |||
| 44 - 47 | 26.vi | 26.ii | 26.6 | 28.iv | 26.6 | 23.4 | |||
| Full-term pregnancies | |||||||||
| None | xvi.five | 31.7 | <0.001 | 17.one | 36.0 | <0.001 | 15.9 | 25.9 | 0.04 |
| 1 – 2 | 57.7 | fifty.0 | 56.8 | 50.iv | 58.9 | 49.three | |||
| ≥3 | 25.6 | 18.5 | 26.i | 13.6 | 25.1 | 24.ix | |||
| Cesarean deliveries* | |||||||||
| None | 69.ix | 68.ii | 0.7 | 67.three | 73.4 | 0.3 | 72.4 | 62.iv | 0.14 |
| 1 | 16.5 | xix.2 | sixteen.4 | xv.4 | xvi.seven | 23.5 | |||
| ≥2 | xiii.half dozen | 12.six | 16.4 | eleven.two | 10.nine | 14.1 | |||
| Oral contraceptive elapsing | |||||||||
| Never | eight.5 | eight.8 | 0.7 | nine.7 | 11.4 | 0.7 | 7.iii | five.6 | 0.4 |
| <one twelvemonth | 11.0 | 11.3 | 13.iii | 9.eight | 8.8 | 13.1 | |||
| 1 year to <5 years | 21.7 | 24.1 | 24.0 | 24.3 | 19.5 | 23.seven | |||
| v years to <10 years ≥10 years | 35.2 | xxx.9 | 32.1 | 30.2 | 38.0 | 31.eight | |||
| Reported history of: | |||||||||
| Tubal ligation | 45.0 | 25.ix | <0.001 | 38.ii | sixteen.3 | <0.001 | 51.7 | 38.3 | 0.007 |
| Infertility | 17.7 | 19.2 | 0.half dozen | 12.half dozen | 16.7 | 0.2 | 22.vii | 22.4 | 0.nine |
| Leiomyomas | 74.4 | 21.6 | <0.001 | 55.8 | 12.9 | <0.001 | 92.8 | 33.2 | <0.001 |
| Endometriosis | 15.iii | 8.7 | 0.002 | 21.1 | eight.0 | <0.001 | 9.7 | 9.half-dozen | 0.9 |
| Myomectomy | 9.9 | iii.vii | <0.001 | four.5 | two.3 | 0.2 | xv.0 | v.5 | 0.002 |
| Polycystic ovary syndrome | two.5 | 2.viii | 0.9 | 3.v | three.four | 0.ix | 1.v | 2.0 | 0.seven |
| Ovarian cysts | 32.2 | 18.2 | <0.001 | 42.7 | twenty.ix | <0.001 | 22.2 | xiv.5 | 0.04 |
| | |||||||||
| Body mass index (kg/g2) | 22.7 | 32.5 | 0.001 | 34.ix | 45.vi | 0.04 | 11.2 | 15.4 | 0.three |
| <25 | 25.9 | 26.9 | 28.2 | 27.0 | 23.8 | 26.nine | |||
| 25 to <30 | 51.4 | 40.v | 36.9 | 27.four | 65.0 | 57.7 | |||
| ≥30 | 51.4 | 40.5 | 36.9 | 27.4 | 65.0 | 57.7 | |||
| Smoking status | |||||||||
| Never | 60.0 | 67.i | 0.09 | 57.8 | 67.0 | 0.1 | 63.three | 67.ii | 0.5 |
| Old smoker | 19.v | 18.i | 24.6 | 20.1 | xiv.five | 15.iv | |||
| Current smoker | twenty.0 | 14.8 | 17.6 | 12.9 | 22.2 | 17.4 | |||
| Age at menarche (years), mean (SD) | twenty.0 | 14.8 | 17.half-dozen | 12.six | 22.2 | 17.4 | |||
| BMI (kg/m2), mean (SD) | 31.iii (7.8) | 29.seven (8.2) | 0.01 | 28.vi (6.6) | 27.4 (6.vii) | 0.05 | 33.7 (8.0) | 33.0 | 0.3 |
| FSH IU/L (at baseline), mean (SD) | 7.ii (5.9) | 7.5 (5.viii) | 0.4 | 7.0(vi.0) | 7.2(5.7) | 0.7 | 7.three(5.viii) | 8.0 (6.0) | 0.3 |
Clinical characteristics of the women with hysterectomies stratified by race are shown in Tabular array ii. The mean uterine weight amidst African American women was more than double that of non-African American women (459 versus 211 grams, p<0.0001). African American women were more probable to undergo intestinal hysterectomy. No statistically pregnant differences were observed in the organs removed at surgery, although a slightly higher proportion of the non-African American women had supracervical hysterectomies or hysterectomies with unilateral oophorectomy. Fibroids and menorrhagia/dysfunctional uterine bleeding were the most common operative diagnoses reported for both African American and non-African American women. Withal, racial differences in the frequency of diagnoses were observed, with African American women more likely to have a diagnosis of fibroids whereas non-African American women were more than probable to have endometriosis or pelvic organ prolapse.
Table 2
Clinical Characteristics of Women Undergoing Hysterectomy, Stratified by Race
| Non-African American Women (northward=199) | African American Women (n=207) | ||||
|---|---|---|---|---|---|
| | |||||
| northward | (%) | n | (%) | P | |
| Blazon of hysterectomy | |||||
| Intestinal | 85 | (42.9) | 141 | (68.i) | <0.001 |
| Vaginal | 94 | (47.5) | 58 | (28.0) | |
| Laparoscopic | 19 | (ix.six) | 8 | (3.9) | |
| Organs removed | |||||
| Uterus simply | 20 | (10.ane) | 11 | (five.3) | 0.1 |
| Uterus, neck | 146 | (73.4) | 171 | (82.vi) | |
| Uterus, i ovary | 3 | (one.five) | 2 | (i.0) | |
| Uterus, cervix, one ovary | 30 | (15.1) | 23 | (11.i) | |
| Postoperative diagnosis* | |||||
| Leiomyomas | 90 | (45.2) | 178 | (86.0) | <0.001 |
| Dysmenorrhea | 37 | (18.6) | 36 | (17.four) | 0.8 |
| Menorrhagia/dysfunctional uterine bleeding | 127 | (63.eight) | 140 | (67.6) | 0.4 |
| Pelvic pain | twenty | (ten.one) | 8 | (3.9) | 0.01 |
| Endometriosis | 23 | (11.6) | 3 | (i.iv) | <0.00 |
| Pelvic organ prolapse | 2 | (1.0) | 0 | (0.0) | 0.1 |
| Endometrial hyperplasia | seven | (3.5) | 3 | (1.4) | 0.ii |
| Cervical dysplasia/carcinoma in situ Adenomyosis | iii | (ane.5) | five | (two.4) | 0.5 |
| | |||||
| Uterine weight (thou), hateful (SD) | 210.eight | (272.four) | 458.v | (431.seven) | <0.001 |
| Hemoglobin, mean (SD) | 12.9 | (i.5) | 11.8 | (1.7) | <0.001 |
| Baseline FSH (IU/L), mean (SD) | vii.0 | (6.0) | vii.3 | (five.8) | 0.7 |
In Figure 1, the Kaplan-Meier curves depict the risk for ovarian failure (defined on the basis of an FSH value ≥ xl IU/L) comparing women with hysterectomy to controls. During ii,410 person-years of follow-up, 106 women experienced ovarian failure, threescore of the women with hysterectomy and 46 of the control women.
Kaplan-Meier plot showing the probability of not experiencing ovarian failure over years of follow-up for women with hysterectomy (solid line) and control women (dashed line). P-value for divergence between hysterectomy and control grouping is <.001 by log-rank test.
Tabular array 3 presents hazard ratios derived from proportional hazards models for ovarian failure by hysterectomy status. The run a risk ratio for ovarian failure among the women with hysterectomy as compared to controls was 1.92, 95% CI one.29 – 2.86, adjusting for age, race, BMI, smoking status and number of pregnancies. Farther, the model estimated that after four years of follow-up, ovarian failure occurred among 14.eight% (95% CI 8.6 – twenty.7%) of the women with hysterectomy and 8.0% (95% CI 4.4 – 11.6%) of the control women. Other statistically significant predictors of menopause in the multivariable model were age (HR per year i.36, 95% CI 1.27 – one.46) and race (HR for non-AA vs. AA 0.59, 95% CI 0.39 – 0.90). As compared to women who had a hysterectomy with both ovaries left intact, the risk was higher for women who had a unilateral oophorectomy along with their hysterectomy.
Tabular array 3
Run a risk Ratios and 95% Confidence Intervals for Ovarian Failure, Defined every bit Follicle-Stimulating Hormone Greater Than 40 IU/Fifty, by Hysterectomy Status, Overall and Within Subgroups
| Run a risk Ratio* | 95% Confidence Interval | P | |
|---|---|---|---|
| All women | |||
| Controls | 1 | Reference | |
| Hysterectomy (all) | 1.92 | 1.29 – two.86 | 0.001 |
| Hysterectomy only | one.74 | one.14 – 2.65 | 0.01 |
| Hysterectomy with unilateral oophorectomy | 2.93 | 1.57 – v.49 | 0.001 |
| African American women | |||
| Controls | 1 | Reference | |
| Hysterectomy (all) | ane.58 | 0.92 – 2.72 | 0.1 |
| Hysterectomy only | 1.43 | 0.81 – 2.53 | 0.2 |
| Hysterectomy with unilateral oophorectomy | ii.74 | ane.10 – 6.87 | 0.03 |
| Non-African American women | |||
| Controls | 1 | Reference | |
| Hysterectomy (all) | 2.66 | 1.47 – 4.81 | 0.001 |
| Hysterectomy only | 2.48 | one.30 – 4.74 | 0.01 |
| Hysterectomy with unilateral oophorectomy | 3.nineteen | one.34 – 7.threescore | 0.01 |
| Women aged forty years and older | |||
| Controls | 1 | Reference | |
| Hysterectomy (all) | 1.79 | ane.18 – 2.71 | 0.006 |
| Hysterectomy only | 1.65 | 1.06 – 2.57 | 0.03 |
| Hysterectomy with unilateral oophorectomy | ii.49 | 1.27 – 4.87 | 0.01 |
| Women aged younger than xl years | |||
| Controls | 1 | Reference | |
| Hysterectomy (all) | four.29 | 0.83 – 22.26 | 0.08 |
| Hysterectomy simply | three.eleven | 0.55 – 17.threescore | 0.two |
| Hysterectomy with unilateral oophorectomy | nineteen.17 | ii.15 – 171.2 | 0.01 |
We also used the model to summate the difference in time when a given proportion of women in each group experienced ovarian failure every bit an guess of how much earlier ovarian failure occurred amidst women with hysterectomy. The fourth dimension difference between when 15% of the women in the command group and the hysterectomy grouping experienced ovarian failure was 1.88 years (95% CI 1.39 – 2.37). Although the study was not powered for sub-group analyses, nosotros did exploratory analyses to examine risk for ovarian failure by hysterectomy status within race and historic period categories. In race-specific analyses, the multivariable-adjusted gamble ratio associated with hysterectomy was ii.66, 95% CI 1.47 – 4.81 for non-African American women and 1.58, 95% CI 0.92 – ii.72 for African American women. A test for interaction of race by hysterectomy condition was non statistically meaning. We as well performed analyses within age strata (< forty years and ≥ 40 years at baseline) to compare risk among groups of women who were earlier or later in their reproductive life. The adventure ratio for the younger women was markedly higher, albeit with a wide confidence interval, than for the older women (Hour=iv.29, 95% CI 0.83 – 22.3 and Hour=1.79, 95% CI 1.18 – 2.71, respectively). The wide confidence interval for the younger women reflects the pocket-size number of events in this age range (vii instances of ovarian failure among women with hysterectomy versus 2 among controls).
Discussion
This report found a virtually twofold increased adventure for ovarian failure amongst women undergoing hysterectomy without bilateral oophorectomy as compared to women of similar age with intact uteri. In race-specific analyses, nosotros found hazard ratios for non-African American women were higher than for African American women only tests for interaction betwixt race and hysterectomy status were non statistically meaning. Comparisons of Kaplan-Meier curves suggest that the increased risk was not due to an sharp disruption of ovarian office afterwards surgery, merely rather a proportional backlog risk throughout the period of follow-upwards.
When our report was designed, we used age-specific estimates of the chance for menopause (24) and the age distribution of women in our study to projection that approximately xi% of the control women would feel ovarian failure during approximately four years of follow-up. Based on the proportional hazards model, we estimated that ovarian failure occurred in approximately eight% of the control women by iv years of follow-up. The 60 minutes of ane.92 for women with hysterectomy corresponds to approximately xv% of women experiencing ovarian failure inside 4 years of hysterectomy.
Nosotros also used the proportional hazards model to estimate that the deviation in fourth dimension to ovarian failure between women with and without hysterectomy was approximately 1.88 years, based on the fourth dimension in which approximately fifteen% of the women in each group experienced ovarian failure. While a nearly two-year divergence in historic period at ovarian failure is clinically important, these data should be interpreted cautiously considering of the limited duration of follow-up of our report population. We do not have the information to conclude that this departure in time to ovarian failure would remain constant between the groups with further follow-upwards.
Our findings are generally consistent with the only other long-term, prospective study of ovarian function afterward hysterectomy in which serial hormone measurements were performed and there was a control group of women from the general population.(20) Farquhar and colleagues also reported an increased adventure for ovarian failure among women with hysterectomy that was more pronounced for women having unilateral oophorectomy; however their gauge of the deviation in time when 15% of women in each grouping experienced ovarian failure was three.7 years, compared to our estimate of i.88 years.(20)
Other recent studies that have examined risk of ovarian failure after hysterectomy accept been inconsistent in their conclusions, with two studies reporting no issue (19, 21) while another reported an adverse effect of hysterectomy on ovarian function (22). However, considering these studies either had no control group (xix) or compared women with hysterectomy to women with uterine artery embolization (21, 22), the results are not strictly comparable to our study.
The strengths of our study include its large sample size, prospective blueprint, serial measurements of hormone levels and the inclusion of large numbers of African American women. African American women have the highest rates of hysterectomy of any racial group within the U.S., with the about striking differences in rates during the mid to tardily pre-menopausal years (35 to 44 years) when their rates are one and half times those of White women.(5)
A limitation of our analysis is the apply of FSH as a marker of ovarian failure. Although FSH is the biomarker most commonly used to categorize menopausal status, information technology is well-recognized that in that location is no cut-point that absolutely distinguishes pre-menopausal from mail-menopausal women.(25) A value of 40 IU/Fifty, which is usually used in the menopause literature, is a very specific simply less sensitive indicator of ovarian failure. Few pre-menopausal women volition accept an FSH value >40 IU/L, but some mail service-menopausal women will have lower FSH values. Using a cut-point of twenty or 30 IU/L would probable have increased sensitivity, but more pre-menopausal women would take been classified incorrectly as having ovarian failure. The misclassification of pre-menopausal women using a lower cutting-signal of FSH is a particular problem in a study of women with hysterectomy where it is not possible to time the claret draw around the menstrual bicycle to ensure drove during the follicular phase. Consequently, it would have been hard to differentiate if moderately high FSH values were indicative of menopause or the mid-bicycle spike indicative of ovulation. Although using a FSH value of 40 IU/50 undoubtedly misclassified some post-menopausal women every bit pre-menopausal, the stringent definition of menopause probably resulted in a conservative estimate of the likelihood of ovarian failure in the written report population.
Another potential limitation of our report was the utilize of volunteers from the same wellness organization as controls. We do not believe that the results were significantly influenced by our choice of command subjects since the study participants were unaware of the study hypothesis and the upshot was based on a biological measure out. Observed differences in baseline characteristics between women with hysterectomies and controls are consistent with chance factors for hysterectomy reported in other studies including college BMI, more pregnancies, and a history of tubal ligation.(26-28) The furnishings on risk of ovarian failure of these and other potential confounders were evaluated and those that were significantly associated with ovarian failure were controlled for in the proportional hazards models. Well-nigh chiefly, the baseline FSH values were not statistically significantly unlike between the women having hysterectomies and the command women (vii.2 and seven.five IU/L, respectively, p=0.4), indicating the comparability of our groups at baseline.
Our findings are consistent with the long-standing hypothesis that women with hysterectomy experience ovarian failure at a younger age.(8) While there is now compelling evidence from two big prospective studies comparing FSH levels in women with hysterectomies and controls to back up this impression, the causal pathways remain unknown. I of the most prominent hypotheses is that the surgery to remove the uterus compromises the blood catamenia to the ovaries, which could outcome in reduced production of hormones leading to before ovarian failure.(eight, 29) The evidence for this mechanism is mixed, with most merely not all studies finding a reduction in ovarian blood menstruation after hysterectomy.(xxx-33) Some other hypothesis is that the uterus has an inhibitory influence of pituitary FSH secretions and consequently has an effect on follicular atresia.(29) It is posited that removal of the uterus allows FSH levels to rise and accelerates follicular depletion, leading to earlier menopause.
An culling explanation for the before menopause observed among women undergoing hysterectomy is that it is not the surgery itself but the status that led to the surgery that places women at increased risk for early ovarian failure. There are scant data on the take chances of ovarian failure associated with mutual indications for hysterectomy such every bit dysfunctional uterine bleeding, fibroids or endometriosis. Information technology is possible that certain cases of dysfunctional uterine bleeding that lead to hysterectomy are a more farthermost manifestation of the menstrual changes that many women experience in the months or years preceding natural menopause. Whether other common indications for hysterectomy such as fibroids or endometriosis also could be associated with increased gamble for early menopause is unknown. Indirect testify based on decreased hazard of fracture or higher bone mineral density among women with a history of fibroids suggests that estrogen levels and by extension, ovarian part, may be higher amidst women with fibroids,(34, 35) which would argue against women with fibroids existence at higher risk for early ovarian failure.
The possibility that the increased gamble for ovarian failure is due to the underlying condition leading to hysterectomy cannot be adequately addressed with the information currently bachelor from this written report. An important area for future inquiry is the evaluation of ovarian reserve comparing women undergoing hysterectomy to command women. Anti-Müllerian hormone (AMH) has been proposed as a useful marking of ovarian reserve and possible predictor of age at menopause. (36) AMH levels correlate with antral follicle counts, exhibit near-linear declines after approximately age thirty and show footling variability throughout the menstrual wheel. Repeated measurements of AMH before and after hysterectomy may be a useful tool for sorting out whether it is the indication for hysterectomy or the surgery itself that places women at higher risk for early on menopause. A comparison of baseline AMH levels in women undergoing hysterectomy and control women would give insight into whether women undergoing hysterectomy (or women with specific indications for hysterectomy) take lower ovarian reserve every bit compared to women of similar historic period. Serial measurements that compare the rate of change in AMH levels over time betwixt women with hysterectomy and controls could requite an indication of whether removal of the uterus accelerates the rate of reject in ovarian reserve.
The major finding from our report is that women undergoing hysterectomy are at significantly increased risk for earlier ovarian failure as measured by serum FSH levels. While it is unresolved whether information technology is the surgery itself or the underlying condition leading to hysterectomy that is the crusade of earlier ovarian failure, it is important that physicians consider this possible sequela when discussing with patients options for handling of benign conditions of the uterus. In add-on, because not all women will feel overt symptoms of menopause, women who have undergone premenopausal hysterectomy may warrant closer monitoring of bone density or cardiovascular risk factors because of their possible risk of early on ovarian failure.
Acknowledgments
Supported by grants from the National Institutes of Health, National Institute on Crumbling (R01 AG020162) and National Center for Inquiry Resources (UL1 RR024128-01).
Footnotes
Financial Disclosure: The authors did not written report any potential conflicts of interest.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223258/
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